Asbestos has been used in the service of humanity for millennia, mostly as an insulator against heat and fire. Though serious health effects were observed in asbestos miners since the first Century AD, its popularity and usage continued, and production accelerated during modern industrialisation, with over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies found that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, resulting in a downturn in its mining and usage in many countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure. Though malignant mesothelioma is classified as an orphan disease, it has resisted all kinds of treatments and drugs over the past decades. Today, newer ideas and practices are being employed against this insidious disease. This short review will summarise the main approaches that attempt to overcome malignant mesothelioma, namely drug repurposing, changes in expression of microRNAs, and immunotherapies. Success is evasive with only moderate success in ameliorating mesothelioma in too few instances. Many research and clinical endeavours are continuing in an effort to find preventative or curative potential treatments for malignant mesothelioma.